The Prediction Of Retained Intron And The Analysis Of The Relationship Between Alternative Splicing And Protein Structure Diversity

Pre-mRNA alternative splicing of Multi-exon gene is a very common regulatorymechanism of gene expression in eukaryotes. One gene can produce multiple RNAtranscripts and further translating into different protein, thus increasing the diversity ofprotein. Distinguishing the type of alternative splicing efficiently and accurately plays animportant role in the study of alternative splicing. The correlation between alternativesplicing and the diversity of protein structure is a crucial part of illuminating mechanismof alternative splicing, and it also has a guiding significance to the study of human’sdisease.This paper mainly studies the following two aspects:(1) The data of human introns’ information was downloaded from ASTD databaseand divided into retaining intron and constitutive intron. Firstly, we analyse the statisticsof the introns’ length and the distribution of introns’ length. The results show that theproportion of which their length between100bp and200bp is the largest among allretaining introns, suggesting that splicing efficiency is related to the length of the introns.Then we use the quadratic discriminant method of combining diversity index based onk-mer(k=1…5) information to distinguish the retaining intron and the constitutive intron.All the predicting accuracy, sensitivity and specificity of5-fold cross-validation aregreater than70%.(2) We has builded an alternative splicing protein isoforms with determinedthree-dimensional structures database based on literature mining、Ensembel database andPDB database from the aspect of protein structural difference and structural stability. Wemake a comparative analysis between morbigenous and the non-morbigenous proteinvariants of alternative splicing;meanwhile, we has builded a real and random alternativesplicing dataset, defining the increment of protein diversity and hydrophobicnon-uniformity and studying non-randomised of alternative splicing events. The study ofalternative splicing and protein structural diversity indicates that although the alternative splicing events of which produce large difference of protein structure tending to causediseases, but the majority of existing alternative splicing events tend to increase thediversity of protein structure, comparing with random splicing events.We proposed a dynamic balance of positive and negative selection pressureshypothesis to explain the result: the positive selection pressure which is associated withlife activities facilitates the increase of protein structural diversity and the fixation ofalternative splicing events in population. While the negative selection pressure restrictsthe scale of which alternative splicing changes the protein structure. Present alternativesplicing event in life is the result of retaining a dynamic balance between positive andnegative selection pressure.